CAN-BIND-17: Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)

Sponsor

University Health Network, Toronto (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05017311

Collaborator

Unity Health Toronto (Other), Baycrest (Other), Centre for Addiction and Mental Health (Other), McMaster University (Other), Queen's University (Other), University of Ottawa (Other), University of British Columbia (Other), University of Calgary (Other), McGill University (Other), Dalhousie University (Other), University of Michigan (Other), Simon Fraser University (Other)

400

Enrollment

Locations

Arms

Anticipated Duration (Months)

66.7

Patients Per Site

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a study that will test a predictive biomarker algorithm based on results from a previous study. The goal of this study is to integrate clinical, imaging, EEG, and molecular data across 8 sites to predict treatment outcome for patients experiencing a major depressive episode (MDE).

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Escitalopram Drug: Brexpiprazole	Phase 4

Detailed Description

This is a multi-site, randomized study with two treatment phases: a double-blind primary treatment phase of 8 weeks, and an open-label secondary extension phase of 4 weeks. This study aims to test a predictive biomarker algorithm to select medication treatment for patients with major depressive disorder (MDD) based on results from the recently completed Canadian Biomarker Integration Network in Depression (CAN-BIND)-1 study. This will be accomplished through collection of clinical, neurophysiological, and molecular measures from both MDD patients and healthy controls. This is not a study to evaluate efficacy of medications; medications in this study have been approved by Health Canada and are widely used for the treatment of MDD.

In this study, individuals diagnosed with MDD in a current major depressive episode (MDE) will be randomly assigned to one of the two treatment groups: Personalized Assignment group or Random Assignment group. Patients in the Random Assignment group will randomly receive open-label escitalopram with the addition of either blinded placebo or brexpiprazole for 8 weeks. Patients in the Personalized Assignment group will receive open-label escitalopram with the addition of either placebo or blinded brexpiprazole for 8 weeks depending on what the predictive biomarker algorithm suggests.

At Week 8, participants will be assessed for treatment response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale score). All patients who initially received both open-label escitalopram and blinded brexpiprazole (regardless of treatment group) will continue to receive these medications for another 4 weeks but the brexpiprazole will no longer be blinded. For those patients who initially received open-label escitalopram and blinded placebo (regardless of treatment group), nonresponders will receive open-label escitalopram and open-label brexpiprazole for another 4 weeks and responders will receive open-label escitalopram only for another 4 weeks.

Over the 12 weeks, participants will attend 7 study visits where they will complete clinical assessments (clinician administered and self-report) and cognitive tests; provide blood, urine, and stool samples; undergo neuroimaging procedures (MRI and EEG); and provide speech samples. At the end of the study, modeling methods will be used to integrate data from these measures to determine the features that best predict treatment outcome.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)

Anticipated Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Allocation by Predictive Biomarker Algorithm; Escitalopram + Brexpiprazole Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted as non-responders to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.	Drug: Escitalopram All patients will receive open-label escitalopram (10-20 mg/d) for the entire study duration (12 weeks). Other Names: Cipralex Drug: Brexpiprazole Depending on the initial randomization process, patients will either receive blinded brexpiprazole (0.5-2 mg/d) for the entire study duration (12 weeks) or for the last 4 weeks of the study if they received the placebo during the first 8 weeks of the study and were non-responders. Other Names: Rexulti
Placebo Comparator: Allocation by Predictive Biomarker Algorithm; Placebo Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted to respond to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.	Drug: Escitalopram All patients will receive open-label escitalopram (10-20 mg/d) for the entire study duration (12 weeks). Other Names: Cipralex
Active Comparator: Random Allocation; Escitalopram + Brexpiprazole Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.	Drug: Escitalopram All patients will receive open-label escitalopram (10-20 mg/d) for the entire study duration (12 weeks). Other Names: Cipralex Drug: Brexpiprazole Depending on the initial randomization process, patients will either receive blinded brexpiprazole (0.5-2 mg/d) for the entire study duration (12 weeks) or for the last 4 weeks of the study if they received the placebo during the first 8 weeks of the study and were non-responders. Other Names: Rexulti
Placebo Comparator: Random Allocation; Placebo Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.	Drug: Escitalopram All patients will receive open-label escitalopram (10-20 mg/d) for the entire study duration (12 weeks). Other Names: Cipralex

Outcome Measures

Primary Outcome Measures

Change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline [Baseline to Week 8]
Measured as clinical response, defined as a decrease in Montgomery Asberg Depression Rating Scale (MADRS) score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit (i.e., lower MADRS scores = better outcome)

Secondary Outcome Measures

Clinical response [Baseline to Week 8]
Defined as a decrease in MADRS score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit
Time to clinical response [Baseline to Week 8]
Defined as time (i.e., number of weeks) to achieve clinical response (i.e., decrease in MADRS score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit)
Remission at Week 8 [Week 8]
Defined as MADRS score ≤10 at Week 8

Other Outcome Measures

Week 12 clinical outcome - Response [Baseline to Week 8 and Week 8 to Week 12]
Response at Week 12 - defined as a decrease in MADRS score at the Week 12 visit, by 50% or greater, from MADRS score at Baseline visit and Week 8
Week 12 clinical outcome - Remission [Week 12]
Defined as MADRS score ≤10 at Week 12

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Patients

Inclusion Criteria:

Outpatients 18 to 60 years of age.
Meet DSM-5 criteria for MDE in MDD as determined by the MINI.
Episode duration ≥ 3 months.
Free of psychotropic medications for at least 5 half-lives (e.g. 1 week for most antidepressants, 5 weeks for fluoxetine) before baseline Visit 1.
MADRS score ≥ 24.
Fluency in English, sufficient to complete the interviews and self-report questionnaires.

Exclusion Criteria:

Any diagnosis, other than MDD, that is considered the primary diagnosis.
Bipolar I or Bipolar-II diagnosis.
Presence of a significant Axis II diagnosis (borderline, antisocial).
High suicidal risk, defined by clinician judgment.
Substance dependence/abuse in the past 6 months.
Presence of significant neurological disorders, head trauma, or other unstable medical conditions.
Pregnant or breastfeeding.
Failure of 4 or more adequate pharmacologic interventions (as determined by the Antidepressant Treatment History Form).
Started psychological treatment within the past 3 months with the intent of continuing treatment.
Patients who have previously failed escitalopram or showed intolerance to escitalopram or brexpiprazole, and patients at risk for hypomanic switch (i.e. with a history of antidepressant induced hypomania).

Healthy Comparison (HC) Participants

Inclusion Criteria:

18 to 60 years of age.
No history of psychiatric disorders (as determined by the modified MINI v.6.0.) or significant physical conditions (e.g. arthritis, fibromyalgia).
Fluency in English, sufficient to complete the interviews and self-report questionnaires.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Calgary	Calgary	Alberta	Canada	T2N 2T9
2	University of British Columbia	Vancouver	British Columbia	Canada	V6T2A1
3	McMaster University	Hamilton	Ontario	Canada	L8P3B6
4	Queen's University	Kingston	Ontario	Canada	K7L4X3
5	University Health Network	Toronto	Ontario	Canada	M5T2S8
6	Centre for Addiction and Mental Health	Toronto	Ontario	Canada	M6J1H4

Investigators

Principal Investigator: Sidney H Kennedy, MD, University Health Network, St. Michael's University, University of Toronto

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Sidney Kennedy, Professor of Psychiatry, University of Toronto, Arthur Sommer Rotenberg Chair in Suicide & Depression Studies, St. Michael's Hospital, Principal Investigator, Canadian Biomarker Integration Network for Depression, University Health Network, University Health Network, Toronto

ClinicalTrials.gov Identifier:

NCT05017311

Other Study ID Numbers:

Pending

First Posted:

Aug 23, 2021

Last Update Posted:

Sep 5, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Sidney Kennedy, Professor of Psychiatry, University of Toronto, Arthur Sommer Rotenberg Chair in Suicide & Depression Studies, St. Michael's Hospital, Principal Investigator, Canadian Biomarker Integration Network for Depression, University Health Network, University Health Network, Toronto

major depression

major depressive disorder

Additional relevant MeSH terms:

Depression

Depressive Disorder